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Heparinase III and methods of specifically cleaving therewith
7455986 Heparinase III and methods of specifically cleaving therewith
Patent Drawings:Drawing: 7455986-10    Drawing: 7455986-11    Drawing: 7455986-12    Drawing: 7455986-13    Drawing: 7455986-14    Drawing: 7455986-15    Drawing: 7455986-16    Drawing: 7455986-17    Drawing: 7455986-18    Drawing: 7455986-19    
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Inventor: Liu, et al.
Date Issued: November 25, 2008
Application: 11/187,571
Filed: July 22, 2005
Inventors: Liu; Dongfang (Yorktown Heights, NY)
Pojasek; Kevin (Cambridge, MA)
Shriver; Zachary (Boston, MA)
Holley; Kristine (Boston, MA)
El-Shabrawi; Yosuf (Graz, AT)
Venkataraman; Ganesh (Bedford, MA)
Sasisekharan; Ram (Bedford, MA)
Assignee: Massachusetts Institute of Technology, Inc. (Cambridge, MA)
Primary Examiner: Swope; Sheridan
Assistant Examiner:
Attorney Or Agent: Wolf Greenfield & Sacks, P.C.
U.S. Class: 435/41
Field Of Search:
International Class: C12P 1/00
U.S Patent Documents:
Foreign Patent Documents: 0 140 781; 0 114 589; 0 244 236; 0 394 971; 0 433 225; 0 342 215; 0 557 887; WO 92/01003; WO 93/05167; WO 93/08289; WO 93/10450; WO 93/15406; WO 93/19096; WO 93/19734; WO 94/12618; WO 94/21689; WO 95/13830; WO 95/34635; WO 96/01648; WO 97/06783; WO 97/11684; WO 97/16556; WO 98/04902; WO 00/12726; WO 00/65521; WO 06/105313; WO 06/105315; WO 07/044471
Other References: Venkataraman et al, Sequencing complex polysaccharides. Science. Oct. 15, 1999;286(5439):537-42. cited by examiner.
Galye et al, Identification of regions in interleukin-1 alpha important for activity. J Biol Chem. Oct. 15, 1993 ;268(29):22105-11. cited by examiner.
Whisstock et al, Prediction of protein function sequence and structure. Q Rev Biophys. Aug. 2003;36(3):307-40. Review. cited by examiner.
USPTO In House alignment CHU27586 from Su et al, Appl Environ Microbiol. Aug. 1996; 62(8): 2723-2734. Alignment with SEQ ID No. 2. cited by examiner.
USPTO in house aligment NCBI Acc No. AAB18278 from Su et al, 1996 with SEQ ID No. 2. cited by examiner.
[No Author Listed] GENBANK Submission; NIH/NCBI, Accession No. 171365. Printed Aug. 20, 2007. cited by other.
Alderman et al., Continuous subcutaneous heparin infusion for treatment of Trousseau's syndrome. Ann Pharmacother. Jul.-Aug. 1995;29(7-8):710-3. cited by other.
Ameer et al., A new approach to regional heparinization: design and development of a novel immobilized heparinase device. Blood Purification Meeting Information: The International Conference on Continuous Renal Replacement Therapies.1998;16(2):107-18. Abstract only. cited by other.
Baumann et al., Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a two-domain protein with a calcium binding parallel beta roll motif. EMBO J. Sep. 1993;12(9):3357-64. cited by other.
Becker et al., Proliferation of human malignant melanomas is inhibited by antisense oligodeoxynucleotides targeted against basic fibroblast growth factor. EMBO J. Dec. 1, 1989;8(12):3685-91. cited by other.
Becker et al., Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. Oncogene. Nov. 1992;7(11):2303-13. cited byother.
Bernstein et al., Immobilized heparin lyase system for blood deheparinization. Methods Enzymol. 1988;137:515-29. cited by other.
Berry et al., Distinct heparan sulfate glycosaminoglycans are responsible for mediating fibroblast growth factor-2 biological activity through different fibroblast growth factor receptors. FASEB Journal express article 10.1096/fj.00-0661fje.Published online Apr. 6, 2001. 19 pages. cited by other.
Biemann, Four decades of structure determination by mass spectrometry: from alkaloids to heparin. J Am Soc Mass Spectrom. Nov. 2002;13(11):1254-72. cited by other.
Birck et al., Expression of basic fibroblast growth factor and vascular endothelial growth factor in primary and metastatic melanoma from the same patients. Melanoma Res. Aug. 1999;9(4):375-81. cited by other.
Cardin et al., Molecular modeling of protein-glycosaminoglycan interactions. Arteriosclerosis. Jan.-Feb. 1989;9(1):21-32. cited by other.
Carlson et al., Behavior of antithrombin III isoforms on immobilized heparins. Evidence that the isoforms bind to different numbers of low-affinity heparin sites. J Biol Chem. Feb. 15, 1988;263(5):2187-94. cited by other.
Cohen, The parallel beta helix of pectate lyase C: something to sneeze at. Science. Jun. 4, 1993;260(5113):1444-5. No abstract available. cited by other.
Comfort et al., Immobilized enzyme cellulose hollow fibers: III. Physical properties and in vitro biocompatibility. Biotechnology and Bioengineering. Dec. 1989;34:1383-90. cited by other.
Crum et al., A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science. Dec. 20, 1985;230(4732):1375-8. cited by other.
Desai et al., Specificity studies on the heparin lyases from Flavobacterium heparinum. Biochemistry. Aug. 17, 1993;32(32):8140-5. cited by other.
Dull et al., Lung endothelial heparan sulfates mediate cationic peptide-induced barrier dysfunction: a new role for the glycocalyx. Am J Physiol Lung Cell Mol Physiol. Nov. 2003;285(5):L986-95. cited by other.
Enriquez-Harris et al., Growth factors and the extracellular matrix. Trends Cell Biol. Aug. 1994;4(8):302-3. cited by other.
Ernst et al., Direct evidence for a predominantly exolytic processive mechanism for depolymerization of heparin-like glycosaminoglycans by heparinase I. Proc Natl Acad Sci U S A. Apr. 14, 1998;95(8):4182-7. cited by other.
Ernst et al., Expression in Escherichia coli, purification and characterization of heparinase I from Flavobacterium heparinum. Biochem J. Apr. 15, 1996;315 ( Pt 2):589-97. cited by other.
Ernst et al., Enzymatic degradation of glycosaminoglycans. Crit Rev Biochem Mol Biol. 1995;30(5):387-444. cited by other.
Feingold et al., Conformational aspects of the reaction mechanisms of polysaccharide lyases and epimerases. FEBS Lett. Nov. 2, 1987;223(2):207-11. cited by other.
Fernandez-Trigo et al., Prognostic implications of chemoresistance-sensitivity assays for colorectal and appendiceal cancer. Am J Clin Oncol. Oct. 1995;18(5):454-60. cited by other.
Ferrante et al., Promising new developments in cancer chemotherapy. Cancer Chemother Pharmacol. 1999;43 Suppl:S61-8. cited by other.
Folkman et al., Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone. Science. Aug. 19, 1983;221(4612):719-25. cited by other.
Folkman et al., Steroid hormones and uterine bleeding. American Association for the Advancement of Science Press. 1992:144-58. cited by other.
Folkman et al., Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. Jan. 1995;1(1):27-31. cited by other.
Franklin et al., Pseudomonas aeruginosa AlgG is a polymer level alginate C5-mannuronan epimerases. J Bacteriol. Apr. 1994;176(7):1821-30. cited by other.
Gacesa, Alginate-modifying enzymes. A proposed unified mechanism of action for the lyases and epimerases. FEBS Lett. 1987;212:199-202. cited by other.
Gioldassi et al., Determination of phosphorylated and sulfated linkage-region oligosaccharides in chondroitin / dermatan and heparan sulfate proteoglycans by high performance liquid chromatography. J Liq Chrom Rel Technol. 1999;22(13):1997-2007.cited by other.
Godavarti et al., A comparative analysis of the primary sequences and characteristics of heparinases I, II, and III from Flavobacterium heparinum. Biochem Biophys Res Commun. Dec. 24, 1996;229(3):770-7. cited by other.
Godavarti et al., Heparinase I from Flavobacterium heparinum. Identification of a critical histidine residue essential for catalysis as probed by chemical modification and site-directed mutagenesis. Biochemistry. May 28, 1996;35(21):6846-52. citedby other.
Godavarti et al., Heparinase I from Flavobacterium heparinum. Role of positive charge in enzymatic activity. J Biol Chem. Jan. 2, 1998;273(1):248-55. cited by other.
Godavarti et al., Heparinase III from Flavobacterium heparinum: cloning and recombinant expression in Escherichia coli. Biochem Biophys Res Commun. Aug 23, 1996;225(3):751-8. cited by other.
Guerrini et al., A novel computational approach to integrate NMR spectroscopy and capillary electrophoresis for structure assignment of heparin and heparan sulfate oligosaccharides. Glycobiology. Nov. 2002;12(11):713-9. cited by other.
Guimond et al., Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides. Curr Biol. Nov. 18, 1999;9(22):1343-6. cited by other.
Hamilton et al., Tumour necrosis factor-alpha blockade: a new era for effective management of rheumatoid arthritis. Expert Opin Pharmacother. Jul. 2000;1(5):1041-52. cited by other.
Harenberg et al., Anticoagulant effects and tissue factor pathway inhibitor after intrapulmonary low-molecular-weight heparin. Blood Coagul Fibrinolysis. Jun. 1996;7(4):477-83. cited by other.
Hart, Glycosylation. Curr Opin Cell Biol. Dec. 1992;4(6):1017-23. cited by other.
Hayes, Prototeins. American Scientist, the Magazine of Sigma Xi, the Scientific Research Society. 1998;86(3):216-21. cited by other.
Hennekens et al., Current issues concerning thrombolytic therapy for acute myocardial infarction. J Am Coll Cardiol. Jun. 1995;25(7 Suppl):18S-22S. cited by other.
Holmes et al., Lessons we have learned from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries. J Am Coll Cardiol. Jun. 1995;25(7 Suppl):10S-17S. cited by other.
Horner et al., Heterogeneity of rat skin heparin chains with high affinity for antithrombin. Biochem J. Jun. 15, 1987;244(3):693-8. cited by other.
Huang et al., Low-molecular-weight heparins. Hematol Oncol Clin North Am. Dec. 1998;12(6):1251-81,vi-vii. cited by other.
Jackson et al., Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol Rev. Apr. 1991;71(2):481-539. cited by other.
Jandik et al., Action pattern of polysaccharide lyases on glycosaminoglycans. Glycobiology. Jun. 1994;4(3):289-96. cited by other.
Johnson et al., Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation. FASEB J. Jan. 2004;18(1):188-90. cited by other.
Kakkar et al., Venous thromboembolism and cancer. Baillieres Clin Haematol. Sep. 1998;11(3):675-87. cited by other.
Kanabrocki et al., Heparin as a therapy for atherosclerosis: preliminary observations on the intrapulmonary administration of low-dose heparin in the morning versus evening gauged by its effect on blood variables. Chronobiol Int. 1991;8(3):210-33.cited by other.
Kanabrocki et al., A quest for the relief of atherosclerosis: potential role of intrapulmonary heparin--a hypothesis. Q J Med. Apr. 1992;83(300):259-82. cited by other.
Kapila et al., Mutations in the heparin binding domain of fibronectin in cooperation with the V region induce decreases in pp. 125(FAK) levels plus proteoglycan-mediated apoptosis via caspases. J Biol Chem. Oct. 22, 1999;274(43):30906-13. cited byother.
Keiser et al., Direct isolation and sequencing of specific protein-binding glycosaminoglycans. Nat Med. Jan 2001;7(1):123-8. cited by other.
Kenyon et al., A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci. Jul. 1996;37(8):1625-32. cited by other.
Kishibe et al., Structural requirements of heparan sulfate for the binding to the tumor-derived adhesion factor/angiomodulin that induces cord-like structures to ECV-304 human carcinoma cells. J Biol Chem. May 19, 2000;275(20):15321-9. cited byother.
Kreitz et al., Controlled delivery of therapeutics from microporous membranes. II. In vitro degradation and release of heparin-loaded poly(D,L-lactide-co-glycolide). Biomaterials. Dec. 1997;18(24):1645-51. cited by other.
Kretsinger, Structure and evolution of calcium-modulated proteins. CRC Crit Rev Biochem. 1980;8(2):119-74. cited by other.
Leckband et al., Characterization of the active site of heparinase. Abstracts of Papers Part 1: Fourth Chemical Congress of North America. 1991;202(1):a56. cited by other.
Leckband et al., An approach for the stable immobilization of proteins. Biotechnol Bioeng. 1991;37:227-37. cited by other.
Lewin, Cells obey the laws of physics and chemistry. Genes V. Oxford University Press. 1994; p. 13. cited by other.
Linhardt et al., Polysaccharide lyases. Appl Biochem Biotechnol. Apr. 1986;12(2):135-76. cited by other.
Linhardt et al., Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost. 1999;25 Suppl 3:5-16. cited by other.
Linhardt et al., Examination of the substrate specificity of heparin and heparan sulfate lyases. Biochemistry. Mar. 13, 1990;29(10):2611-7. cited by other.
Linhardt et al., Mapping and quantification of the major oligosaccharide components of heparin. Biochem J. Sep. 15, 1988;254(3):781-7. cited by other.
Liu et al., Strategy for the sequence analysis of heparin. Glycobiology. Dec. 1995;5(8):765-74. cited by other.
Liu et al., Tumor cell surface heparan sulfate as cryptic promoters or inhibitors of tumor growth and metastasis. Proc Natl Acad Sci U S A. Jan. 22, 2002;99(2):568-73. cited by other.
Liu et al., Dynamic regulation of tumor growth and metastasis by heparan sulfate glycosaminoglycans. Semin Thromb Hemost. Feb. 2002;28(1):67-78. cited by other.
Liu et al., Characterization of a heparan sulfate octasaccharide that binds to herpes simplex virus type I glycoprotein D. J Bio Chem. Sep. 6, 2002;277(36):33456-67. Epub Jun. 21, 2002. cited by other.
Liu et al., The calcium-binding sites of heparinase I from Flavobacterium heparinum are essential for enzymatic activity. J Biol Chem. Feb. 12, 1999;274(7):4089-95. cited by other.
Liu et al., Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3A sulfates N-unsubstituted glucosamine residues. J Biol Chem. Dec. 31, 1999;274(53):38155-62. cited by other.
Lohse et al., Purification and characterization of heparin lyases from Flavobacterium heparinum. J Biol Chem. Dec. 5, 1992;267(34):24347-55. cited by other.
Lustig et al., Alternative splicing determines the binding of platelet-derived growth factor (PDGF-AA) to glycosaminoglycans. Biochemistry. Sep. 17, 1996;35(37):12077-85. cited by other.
Marciniak, Differential role of fractionated heparin in antithrombin-III proteolysis. Blood. Mar. 1982;59(3):576-81. cited by other.
McLean et al., Enzymic removal of 2-O-sulphato-.DELTA.4,5-glycuronic acid residues from heparin oligosaccharides. Proceedings of the 7.sup.th International Symposium of Glycoconjugates. Lund, Sweden. 1983;68-9. cited by other.
Miller et al., Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. Sep. 1994;145(3):574-84. cited by other.
Murphy et al., Basic fibroblast growth factor binding and processing by human glioma cells. Mol Cell Endocrinol. Oct. 30, 1995;114(1-2):193-203. cited by other.
Myette et al., Molecular cloning of the heparin/heparan sulfate delta 4,5 unsaturated glycuronidase from Flavobacterium heparinum, its recombinant expression in Escherichia coli, and biochemical determination of its unique substrate specificity.Biochemistry. Jun. 11, 2002;41(23):7424-34. cited by other.
Myette et al., The heparin/heparan sulfate 2-O-sulfatase from Flavobacterium heparinum. Molecular cloning, recombinant expression, and biochemical characterization. J Biol Chem. Apr. 4, 2003;278(14):12157-66. cited by other.
Myette et al., Expression in Escherichia coli, purification and kinetic characterization of human heparan sulfate3-O-sulfotransferase-I. Biochem Biophys Res Commun. Feb. 1, 2002;290(4):1206-13. cited by other.
Natke et al., Heparinase treatment of bovine smooth muscle cells inhibits fibroblast growth factor-2 binding to fibroblast growth factor receptor but not FGF-2 mediated cellular proliferation. Angiogenesis. 1999;3(3):249-57. cited by other.
Nesbit et al., Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes. Oncogene. Nov. 11, 1999;18(47):6469-76. cited by other.
Nesheim et al., Dependence of antithrombin III and thrombin binding stoichiometries and catalytic activity on the molecular weight of affinity-purified heparin. J Biol Chem. Mar. 5, 1986;261(7):3214-21. cited by other.
Nickoloff et al., Aberrant production of interleukin-8 and thrombospondin-I by psoriatic keratinocytes mediates angiogenesis. Amer J Pathol. 1994;144:820-8. cited by other.
Ornitz et al., Receptor specificity of the fibroblast growth factor family. J Biol Chem. Jun. 21, 1996;271(25):15292-7. cited by other.
Padera et al., FGF-2/fibroblast growth factor receptor/heparin-like glycosaminoglycan interactions: a compensation model for FGF-2 signaling. FASEB J. Oct 1999;13(13):1677-87. cited by other.
Patel et al., New chemotherapeutic strategies for soft tissue sarcomas. Semin Surg Oncol. Jul.-Aug. 1999;17(1):47-51. cited by other.
Peacock et al., Angiogenesis inhibition suppresses collagen arthritis. J Exp Med. Apr. 1, 1992;175(4):1135-8. cited by other.
Pixley et al., Preparation of highly stable antithrombin-sepharose and utilization for the fractionation of heparin. Thromb Res. Apr. 15, 1982;26(2):129-33. cited by other.
Prior Art Search, USPTO, Nov. 20, 2006. cited by other.
Pojasek et al., Recombinant expression, purification, and kinetic characterization of chondroitinase AC and chondroitinase B from Flavobacterium heparinum. Biochem Biophys Res Commun. Aug. 17, 2001;286(2):343-51. cited by other.
Pojasek et al., Biochemical characterization of the chondroitinase B active site. J Biol Chem. Aug. 23, 2002;277(34):31179-86. cited by other.
Pojasek et al., Histidine 295 and histidine 510 are crucial for the enzymatic degradation of heparan sulfate by heparinase III. biochemistry. Apr. 11, 2000;39(14):4012-9. cited by other.
Raman et al., Identification of structural motifs and amino acids within the structure of human heparan sulfate 3-O-sulfotransferase that mediate enzymatic function. Biochem Biophys Res Commun. Feb. 1, 2002;290(4):1214-9. cited by other.
Raman et al., The heparin/heparan sulfate 2-O-sulfatase from Flavobacterium heparinum. A structural and biochemical study of the enzyme active site and saccharide substrate specificity. J Biol Chem. Apr. 4, 2003;278(14):12167-74. cited by other.
Rhomberg et al., Mass spectrometric and capillary electrophoretic investigation of the enzymatic degradation of heparin-like glycosaminoglycans. Proc Natl Acad Sci U S A. Apr. 14, 1998;95(8):4176-81. cited by other.
Rhomberg et al., Mass spectrometric sequencing of heparin and heparan sulfate using partial digestion with heparinases. 45.sup.th Annual Conference of Mass Spectrometry Allied Topics. 1997;1026-7. Abstract only. cited by other.
Rhomberg, Mass spectrometric and capillary electrophoretic investigation of heparin, heparinases, and related compounds. MIT (Department of Chemistry) Thesis. 1998. cited by other.
Rhomberg et al., Mass spectrometric evidence for the enzymatic mechanism of the depolymerization of heparin-like glycosaminoglycans by heparinase II. Proc Natl Acad Sci U S A. Oct. 13, 1998;95(21):12232-7. cited by other.
Rodeck et al., Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes. J Invest Dermatol. Jul. 1991;97(1):20-6. cited by other.
Rodriguez-Fernandez et al., Why do so many stimuli induce tyrosine phosphorylation of FAK? Bioessays. Dec. 1999;21(12):1069-75. cited by other.
Rudd et al., Oligosaccharide sequencing technology. Nature. Jul. 10, 1997;388(6638):205-7. cited by other.
Sanderson, Heparan sulfate proteoglycans in invasion and metastasis. Semin Cell Dev Biol Apr. 2001; 12(2);89-98. Review. cited by other.
Sasisekharan et al., Heparin and heparan sulfate: biosynthesis, structure and function. Curr Opin Chem Biol. Dec. 2000;4(6):626-31. cited by other.
Sasisekharan et al., Roles of heparan-sulphate glycosaminoglycans in cancer. Nat Rev Cancer. Jul. 2002:2(7):521-8. cited by other.
Sasisekharan et al., Heparinase I from Flavobacterium heparinum: the role of the cysteine residue in catalysis as probed by chemical modification and site-directed mutagenesis. Biochemistry. Nov. 7, 1995;34(44):14441-8. cited by other.
Sasisekharan et al., Heparinase inhibits neovascularization. Proc Natl Acad Sci U S A. Feb. 15,1994;91(4):1524-8. cited by other.
Sasisekharan et al., Cloning and expression of heparinase I gene from Flavobacterium heparinum. Proc Natl Acad Sci U S A. Apr. 15, 1993;90(8):3660-4. cited by other.
Sasisekharan et al., Heparinase I from Flavobacterium heparinum. Mapping and characterization of the heparin binding domain. J Biol Chem. Feb. 9, 1996;271(6):3124-31. cited by other.
Schlaepfer et al., Signaling through focal adhesion kinase. Prog Biophys Mol Biol. 1999;71(3-4):435-78. cited by other.
Seger et al., The MAPK signaling cascade. FASEB J. Jun. 1995;9(9):726-35. cited by other.
Shriver et al., Emerging views of heparan sulfate glycosaminoglycan structure/activity relationships modulating dynamic biological functions. Trends Cardiovasc Med. Feb. 2002;12(2):71-7. cited by other.
Shriver et al., Heparinase II from Flavobacterium heparinum. Role of cysteine in enzymatic activity as probed by chemical modification and site- directed mutagenesis. J Biol Chem. Sep. 4, 1998;273(36):22904-12. cited by other.
Shriver et al., Heparinase II from Flavobacterium heparinum. Role of histidine residues in enzymatic activity as probed by chemical modification and site-directed mutagenesis. J Biol Chem. Apr. 24, 1998;273(17):10160-7. cited by other.
Shriver et al., Biochemical investigations and mapping of the calcium-binding sites of heparinase I from Flavobacterium heparinum. J Biol Chem. Feb. 12, 1999;274(7):4082-8. cited by other.
Shriver et al., Sequencing of 3-O sulfate containing heparin decasaccharides with a partial antithrombin III binding site. Proc Natl Acad Sci U S A. Sep. 12, 2000;97(19):10359-64. cited by other.
Shriver et al., Cleavage of the antithrombin III binding site in heparin by heparinases and its implication in the generation of low molecular weight heparin. Proc Natl Acad Sci U S A. Sep. 12, 2000;97(19):10365-70. cited by other.
Sievers et al., Clinical studies of new "biologic" approaches to therapy of acute myeloid leukemia with monoclonal antibodies and immunoconjugates. Curr Opin Oncol. Jan. 2000;12(1):30-5. cited by other.
Silver et al., Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo. Eur J Pharmacol. Jun. 12, 1998;351(1):79-83. cited by other.
Solokoff et al., Targeting angiogenic pathways involving tumor-stromal interaction to treat advanced human prostate cancer. Cancer Metastasis Rev. 1998-1999;17(4):307-15. cited by other.
Su et al., Isolation and expression in Escherichia coli of hepB and hepC, genes coding for the glycosaminoglycan-degrading enzymes heparinase II and heparinase III, respectively, from Flavobacterium heparinum. Appl. Environ. Microbiol. 1996 62:2723-2734. cited by other.
Sundaram et al., Rational design of low-molecular weight heparins with improved in vivo activity. Proc Natl Acad Sci U S A. Jan. 21, 2003;100(2):651-6. cited by other.
Takahashi et al., Cellular markers that distinguish the phases of hemangioma during infancy and childhood. J Clin Invest. Jun. 1994;93(6):2357-64. cited by other.
Taylor et al., Protamine is an inhibitor of angiogenesis. Nature. May 27, 1982;297(5864):307-12. cited by other.
Torcia et al., Interferon-alpha-induced inhibition of B16 melanoma cell proliferation: interference with the bFGF autocrine growth circuit. Biochem Biophys Res Commun. Sep. 7, 1999;262(3):838-44. cited by other.
Turnbull et al., Heparan sulfate: decoding a dynamic multifunctional cell regulator. Trends Cell Biol. Feb. 2001;11(2):75-82. cited by other.
Valentine et al., Low-molecular-weight heparin therapy and mortality. Semin Thromb Hemost. 1997;23(2):173-8. cited by other.
Wang et al., Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nat Med. Aug. 1997;3(8):887-93. cited by other.
Weitz, Jeffrey I., Low-Molecular-Weight Heparins. N Engl J Med. Sep. 4, 1997;337(10):688-98. cited by other.
Wishart et al., A single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. J Biol Chem. Nov. 10, 1995;270(45):26782-5. cited by other.
Witkowski et al., Conversion of a beta-ketoacyl synthase to a malonyl decarboxylase by replacement of the active-site cysteine with glutamine. Biochemistry. Sep 7, 1999;38(36):11643-50. cited by other.
Woll et al., Uveal melanoma: natural history and treatment options for metastatic disease. Melanoma Res. Dec. 1999;9(6):575-81. cited by other.
Yamada et al., Structural studies on the bacterial lyase-resistant tetrasaccharides derived from the antithrombin III-binding site of procine intestinal heparin. J Biol Chem. Mar. 5, 1993;268(7):4780-7. cited by other.
Yang et al., Purification and characterization of heparinase from Flavobacterium heparinum. J Biol Chem. Feb. 10, 1985;260(3):1849-57. cited by other.
Yoder et al., New domain motif: the structure of pectate lyase C, a secreted plant virulence factor. Science. Jun. 4, 1993;260(5113):1503-7. cited by other.
Yoder et al., Unusual structural features in the parallel beta-helix in pectate lyases. Structure. Dec. 15, 1993;1(4):241-51. cited by other.
Zacharski et al., Blood coagulation activation in cancer: challenges for cancer treatment. Hamostaseologic. 1995;15:14-20. cited by other.
Zhang et al., 6-O-sulfotransferase-1 represents a critical enzyme in the anticoagulant heparan sulfate biosynthetic pathway. J Biol Chem. Nov. 9, 2001;276(45):42311-21. cited by other.
Zhao et al., Rapid, sensitive structure analysis of oligosaccharides. Proc Natl Acad Sci U S A. Mar. 4, 1997;94(5):1629-33. cited by other.









Abstract: The invention relates to heparinase III and mutants thereof. Modified forms of heparinase III having reduced enzymatic activity which are useful for a variety of purposes, including sequencing of heparin-like glycosaminoglycans (HLGAGs), removing active heparan sulfate from a solution, inhibition of angiogenesis , etc. have been discovered according to the invention. The invention in other aspects relates to methods of treating cancer and inhibiting tumor cell growth and/or metastasis using heparinase III, or products produced by enzymatic cleavage by heparinase III of HLGAGs.
Claim: We claim:

1. A method of cleaving comprising: contacting a linear polysaccharide with a disaccharide repeat unit of a uronic acid [.alpha.-L-iduronic acid (I) or .beta.-D-glucuronic acid (G)]linked 1, 4 to .alpha.-D-hexosamine (H) with a protein comprising a modified heparinase III in vitro, wherein the modified heparinase III has the amino acid sequence of the mature peptide of SEQ ID NO: 2, wherein at least one histidine residue selectedfrom the group consisting of His36, His105, His110, His139, His152, His225, His234, His241, His424, His469, and His539 has been substituted with a residue selected from the group consisting of alanine, serine, tyrosine, threonine, and lysine.

2. The method of claim 1, wherein the modified heparinase III has at least one substitution at a histidine residue selected from the group consisting of His110, His225 and His241.

3. The method of claim 1, wherein the modified heparinase III has a substitution at His110.

4. The method of claim 1, wherein the modified heparinase III has a substitution at His241.

5. The method of claim 1, wherein the modified heparinase III has a substitution at His225.

6. The method of claim 5, wherein the His225 is substituted with alanine.

7. The method of claim 1, wherein the modified heparinase III is in a composition that comprises a pharmaceutically acceptable carrier.

8. The method of claim 1, wherein the modified heparinase III is immobilized on a solid support.

9. The method of claim 8, wherein the solid support is a sheet, test strip, membrane, bead, test tube, microplate well or the external surface of a rod.
Description:
 
 
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